The ongoing progresses in the knowledge of the pathogenic mechanisms of various inflammatory or immune-mediated diseases and the availability of innovative biotechnological approaches have lead to the development of new drugs which add to conventional treatments. TNF-alpha inhibitors (infliximab, adalimumab and etanercept) have demonstrated efficacy either as monotherapy or in combination with other anti-inflammatory or disease modifying anti-rheumatic drugs (DMARDs). The efficacy and safety profile of the TNF-alpha inhibitors can be considered, in general, as a class effect. Nevertheless, some differences may exist among the three agents. In this paper, we will briefly review the indications for the use of the three TNF-alpha inhibitors, the pre-treatment considerations and the reported adverse events.